Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Over the past decade we have reported excellent outcomes in pediatric living-donor liver transplantation (LDLT) with recipient survival exceeding 90%. Principles established in these patients were extended to LDLT in adults. To compare outcomes in donors and recipients between adult and pediatric LDLT in a single center, we reviewed patient records of 45 LDLT performed between 1/98 and 2/01: 23 adult LDLT (54 +/- 6.5 yr) and 22 pediatric LDLT (33.7 +/- 53.5 months). Preoperative liver function was worse in adults (International Normalized Ratio [INR] 1.5 +/- 0.4 vs. INR 1.2 +/- 0.5; p = 0.032). 4 adults (17%) met criteria for status 1 or 2A. Only 1 child was transplanted urgently. Analysis included descriptive statistics and Kaplan-Meier estimation. Donor mortality was 0% with 1 re-exploration, 2.4%. Median hospital stay (LOS) was 6.0 days (range, 4-12 days). Donor morbidity and LOS did not differ by sex, extent of hepatectomy, or adult and pediatric LDLT ( p = 0.49). In contrast, recipient outcomes were worse for adults. Adult 1 year graft survival was 65% (3 retransplants [ReTx], 5 deaths) vs. 91% for children (1 ReTx, 1 death) p = 0.02. Graft losses in adults were due to sepsis (n = 3), small for size (n = 2), suicide, and hepatic artery thrombosis (HAT), whereas in children graft losses were due to portal thrombosis and total parenteral nutrition (TPN) liver failure. Biliary leaks occurred in 22% of adults and 9% of children. Hepatic vein obstruction occurred in 17% of adults and in none of the children. Median LOS was comparable (adult, 16.5 days (range, 7-149 days); child, 17 days (range, 10-56 days), p = 0.2). Graft function (total bilirubin (TBili) < 5mg/dl, INR < 1.2, aspartate aminotransferase (AST) < 100 U/l) normalizing by day 4 in children and by day 14 in adults. Adults fared worse, with an array of problems not seen in children, in particular, hepatic vein obstruction and small-for-size syndrome. Biliary leaks were diagnosed later in adults and were lethal in 3 cases; this was later avoided with biliary drainage in adult recipients. Finally, use of LDLT in decompensated adults led to death in 3 of 4 patients, and should be restricted to elective use.
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PMID:Analysis of failure in living donor liver transplantation: differential outcomes in children and adults. 1260 66

Vibrio vulnificus is the leading cause of death in the United States associated with the consumption of raw seafood, particularly oysters. In epidemiological studies, primary septicemia and inflammation-mediated septic shock caused by V. vulnificus is strongly associated with liver disease, often in the context of chronic alcohol abuse. The present study was undertaken to determine whether clinical biomarkers of liver function or cellular oxidative stress are associated with peripheral blood mononuclear cell inflammatory cytokine responses to V. vulnificus. Levels of interleukin-1 beta (IL-1 beta), IL-6, IL-8, and tumor necrosis factor alpha elicited in response to V. vulnificus and measured in cell supernatants were not associated with the liver biomarkers aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or the AST/ALT ratio. In contrast, reduced glutathione (GSH) levels were associated with the release of all four cytokines (IL-1 beta [R(2) = 0.382; P = 0.006], IL-6 [R(2) = 0.393; P = 0.005], IL-8 [R(2) = 0.487; P = 0.001], and TNF-alpha [R(2) = 0.292; P = 0.021]). Those individuals with below-normal GSH levels produced significantly less proinflammatory cytokines in response to V. vulnificus. We hypothesize that persons with markers for cellular oxidative stress have increased susceptibility to V. vulnificus septicemia.
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PMID:Inflammatory cytokine response to Vibrio vulnificus elicited by peripheral blood mononuclear cells from chronic alcohol users is associated with biomarkers of cellular oxidative stress. 1281 21

The role of endothelin ETA receptors in sepsis-induced mortality and edema formation was evaluated with a selective antagonist ABT-627 [2-(4-methoxyphenyl)-4-(1,3-benzodioxol-5-yl)-1-(N,N-di(n-butyl)amino carbonylmethyl)-pyrrolidine-3-carboxylic acid]. Sprague-Dawley rats received saline (control group), Escherichia coli endotoxin (10 mg/kg, sepsis group) or infusion of ABT-627 prior and immediately after saline and endotoxin injection. Mortality, edema formation (wet/dry ratios), and multiple tissue injury (indicated by serum concentrations of creatinine, urea, bilirubin, creatine kinase, lactate dehydrogenase, and aspartate aminotransferase) were monitored within 5 h. Endotoxin injection elicited 64% mortality, significantly augmented edema formation in liver, heart, lung, and kidney, and raised serum levels of tissue injury markers. Pretreatment with ABT-627 completely reversed endotoxin-induced mortality, significantly attenuated wet/dry ratios of the heart, liver, and kidney, but not lungs, and reduced serum levels of creatine kinase, creatinine, aspartate aminotransferase, and lactate dehydrogenase, but not that of urea and bilirubin. These results suggest that endothelin ETA receptors play a significant role in promoting mortality, edema formation (except in the lungs), and tissue injury in animals with severe sepsis.
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PMID:Role of endothelin ETA receptors in sepsis-induced mortality, vascular leakage, and tissue injury in rats. 1290 4

The liver is one of the major target organs affected in sepsis, and its failure always results in critical consequences. It has been reported that recombinant human interleukin 11 (rhIL-11), a pleiotropic cytokine, may be useful in the treatment of sepsis. However, the effect of IL-11 specifically on the hepatic failure in sepsis has not been evaluated. In the present study, we examined the effect of rhIL-11 on the hepatic injury in a rat endotoxemia model. Acute endotoxemia was induced in male Sprague-Dawley rats by intraperitoneal injection (i.p.) of bacterial lipopolysaccharide (LPS, 20 mg/kg). Immediately after injection of LPS, rats were treated with rhIL-11 (150 microg/kg, i.p.) or the vehicle. LPS treatment induced severe hepatic injury as revealed by marked increases in serum alanine transaminase (ALT) and aspartate transaminase (AST) activities, extensive hepatocyte necrosis, tumor necrosis factor-alpha (TNF-alpha) mRNA, inducible nitric oxide synthase (iNOS) mRNA, and DNA-binding activity of nuclear factor-kappaB (NF-kappaB). In contrast, rhIL-11 treatment significantly ameliorated the LPS-induced hepatic injury, as judged by marked improvement in all these indices. In addition, rhIL-11 treatment markedly decreased LPS-induced mortality. These results indicate that rhIL-11 plays a significant protective role in LPS-induced hepatic injury in acute endotoxemia.
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PMID:A protective role of interleukin 11 on hepatic injury in acute endotoxemia. 1475 86

Several studies have implicated a role of peptidoglycan (PepG) as a pathogenicity factor in sepsis and organ injury, in part by initiating the release of inflammatory mediators. We wanted to elucidate the structural requirements of PepG to trigger inflammatory responses and organ injury. Injection of native PepG into anesthetized rats caused moderate but significant increases in the levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and bilirubin (markers of hepatic injury and/or dysfunction) and creatinine and urea (markers of renal dysfunction) in serum, whereas PepG pretreated with muramidase to digest the glycan backbone failed to do this. In an ex vivo model of human blood, PepG containing different amino acids induced similar levels of the cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), IL-8, and IL-10, as determined by plasma analyses (enzyme-linked immunosorbent assay). Hydrolysis of the Staphylococcus aureus cross-bridge with lysostaphin resulted in moderately reduced release of TNF-alpha, IL-6, IL-8, and IL-10, whereas muramidase digestion nearly abolished the ability to induce cytokine release and IL-6 mRNA accumulation in CD14(+) monocytes compared to intact PepG. However, additional experiments showed that muramidase-treated PepG synergized with lipopolysaccharide to induce TNF-alpha and IL-10 release in whole blood, despite its lack of inflammatory activity when administered alone. Based on these studies, we hypothesize that the structural integrity of the glycan chain of the PepG molecule is very important for the pathogenic effects of PepG. The amino acid composition of PepG, however, does not seem to be essential for the inflammatory properties of the molecule.
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PMID:Organ injury and cytokine release caused by peptidoglycan are dependent on the structural integrity of the glycan chain. 1497 33

In acute-phase response, the use of amino acids is redirected to supporting the synthesis of proteins for host defence and tissue repair. Fibrinogen is one of these proteins, and its plasma levels commonly increase in acute-phase conditions. After hepatectomy, this pattern may be modified by the variable impact of postoperative liver dysfunction. Our study was performed to specifically assess and quantify this aspect. Data were collected prospectively on 82 hepatectomized patients; 62 recovered normally, 20 had major complications (most commonly sepsis). Plasma fibrinogen and a large series of complementary variables were determined preoperatively and at postoperative days 1, 3 and 7 in all patients and until recovery, or death in those with complications. Multiple regression analysis showed that postoperative changes in fibrinogen (deltaFIB, micromol/l) were simultaneously related to the number of resected liver segments (NSEG), total bilirubin (BIL, micromol/l), aspartate aminotransferase (AST, U/l, n.v. 5-45), albumin (ALB, g/l), prothrombin activity (PA, % of standard reference), age (AGE, years) and basal preoperative fibrinogen (PFIB, micromol/l): deltaFIB = -0.51(NSEG) - 0.71(Log(n)BIL) - 0.74(Log(n)AST) + 0.11(ALB) + 0.09(PA) - 0.06(AGE) - 0.55(PFIB) + 7.74 (n=362, r2=0.68, p<0.001). In addition, an early postoperative tendency for low fibrinogen was associated with the subsequent development of complications or death. Our study quantifies the impact of size of hepatectomy and dysfunction of residual liver in modulating postoperative fibrinogen level and suggests that failure of fibrinogen to increase may signal an unfavorable condition limiting up-regulation of acute-phase response and increasing liability to complications.
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PMID:Modulation of plasma fibrinogen levels in acute-phase response after hepatectomy. 1508 May 57

Marginal liver donor criteria included the following: obesity (weight >100 Kg or BMI >27), age >50 years; macrovesicular steatosis >50%; intensive care unit stay >4 days; prolonged hypotensive episodes of >1 hour, and <60 mm Hg with high inotropic drug use (dopamine, [DPM] > 14 microg/kg per minute); cold ischemia time >14 hours, peak serum sodium >155 mEq/L; sepsis, viral infections, and alcoholism; high levels of bilirubin, ALT, and AST, or extrahepatic neoplasia. Between August 1992 and May 2003, we performed 251 liver transplants in 241 patients of whom 155 are presently alive. We used 124 (49.4%) standard donors and 127 (50.6%) marginal donors. Among the group that received a standard donor, 81 (65.3%) are still alive. Among recipients of organs from marginal donors. 81 (63.8%) are still alive. We also assessed the quality of donors according to the severity of recipient disease. For standard donors these outcomes were 61.5% for UNOS 1, 37.5% for UNOS 2A, 73.2% for UNOS 2B, and 80% for UNOS 3 for marginal donors they were 46.1% for UNOS 1, 53.6% for UNOS 2A, 70.7% for UNOS 2B, and 63.6% for UNOS 3. Among the patients who received a liver from a donor >60 years old, there were no survivors in UNOS 1 and 2A, but there were good results in groups 2B and 3. These results suggest there is no difference between marginal and standard donors, even in sick patients, with the exception of donor age.
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PMID:Marginal donors in liver transplantation. 1511 May 80

Bicuculline methiodide attenuates inflammation by inhibiting the production of proinflammatory cytokines, such as tumor necrosis factor-alpha, and by increasing the production of the anti-inflammatory cytokine interleukin-10, both of which play important roles in the pathogenesis of sepsis. The aim of this study was to examine the effects of bicuculline methiodide on sepsis in the cecal ligation and puncture septic-rat model. Cytokine production was measured by enzyme-linked immunosorbent assay. Oxidative stress was assessed by determining serum lipid peroxidation and nitrite levels. Hepatic injury was evaluated by determining the levels of serum aspartate aminotransferase, alkaline phosphatase, and total bilirubin. Mortality was recorded within 24 h. Bicuculline methiodide potently decreased the production of tumor necrosis factor-alpha and interleukin-1beta but increased interleukin-10 in serum. Bicuculline methiodide significantly decreased serum lipid peroxidation and nitrite levels. Further, bicuculline methiodide attenuated hepatic injury and reduced mortality after cecal ligation and puncture. Therefore, the alteration of cytokine production may be involved in the effects of bicuculline methiodide on hepatic injury and mortality in septic rats.
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PMID:Bicuculline methiodide attenuates hepatic injury and decreases mortality in septic rats: role of cytokines. 1537 90

Sepsis is a leading cause of multiorgan dysfunction and death in hospitalized patients. Dysregulated inflammatory processes and apoptosis contribute to the pathogenesis of sepsis-induced organ dysfunction and death. A(1) adenosine receptor (A(1)AR) activation reduces inflammation and apoptosis after ischemia-reperfusion injury. Therefore, we questioned whether A(1)AR-mediated reduction of inflammation and apoptosis could improve mortality and organ dysfunction in a murine model of sepsis. A(1)AR knockout mice (A(1) knockout) and their wild-type (A(1) wild-type) littermate controls were subjected to cecal ligation and double puncture (CLP) with a 20-gauge needle. A(1) knockout mice or A(1) wild-type mice treated with 1,3-dipropyl-8-cyclopentylxanthine (a selective A(1)AR antagonist) had a significantly higher mortality rate compared with A(1) wild-type mice following CLP. Mice lacking endogenous A(1)ARs demonstrated significant elevations in plasma creatinine, alanine aminotransferase, aspartate aminotransferase, keratinocyte-derived chemokine, and tumor necrosis factor-alpha 24 h after induction of sepsis compared with wild-type mice. The renal corticomedullary junction from A(1) knockout mice also exhibited increased myeloperoxidase activity, intercellular adhesion molecule-1 protein, and mRNA encoding proinflammatory cytokines compared with renal samples from A(1) wild-type littermate controls. No difference in renal tubular apoptosis was detected between A(1) knockout and A(1) wild-type mice. We conclude that endogenous A(1)AR activation confers a protective effect in mice from septic peritonitis primarily by attenuating the hyperacute inflammatory response in sepsis.
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PMID:A1 adenosine receptor knockout mice exhibit increased mortality, renal dysfunction, and hepatic injury in murine septic peritonitis. 1578 41

Oxidative stress triggered by septic insult may be the major cause of multiple organ dysfunction syndrome (MODS) in intensive unit care patients. The inducible form of heme oxygenase-1 (HO-1) can be induced by cytokines, lipopolysaccharide, and reactive oxygen species during sepsis. These facts raise the question of whether the expression of HO-1 in leukocytes can indicate the level of oxidative stress of multiple organs in sepsis. Clinical peritonitis was simulated in an animal model by cecal ligation and puncture (CLP). The level of oxidative stress was examined by plasma lipid peroxidation (LPO). Liver function was analyzed by plasma aspartate aminotransferase, alanine aminotransferase, total bilirubin, and direct bilirubin. Lung function was evaluated by severity of edema. Renal function was measured by blood urea nitrogen and creatinine. The correlation between early HO-1 induction and LPO level or organ functional indicators of the same rat at late sepsis was analyzed by linear regression. The results showed that the protein content of HO-1 increased at 9 h after CLP, whereas expression of HO-1 mRNA in leukocytes was significantly increased (P < 0.01) at 6 h after CLP. Plasma level of LPO and the indices of hepatic, pulmonary, and renal function were significantly increased at 18 h after CLP. Moreover, highly negative correlations were observed between HO-1 mRNA expression at 6 h after CLP and level of LPO or severity of hepatic/renal dysfunction at 18 h after CLP. These results suggest that early HO-1 mRNA expression in leukocytes may represent oxidative stress and may predict the severity of liver and renal dysfunction during sepsis.
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PMID:Early expression of heme oxygenase-1 in leukocytes correlates negatively with oxidative stress and predicts hepatic and renal dysfunction at late stage of sepsis. 1583 14


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